Genpharm International, Inc.

Stichting Voor De Technische Wetenschappen

Centraal Diergeneeskundig Instituut

Centraal Diegeneeskundig Instituut

Antonius J Berns

Paulus J Krimpenfort

Arnold Leonard Gielkens

Robertus J Moormann

Maria Madalene Van Zijl

Niels De Wind

Transgenic mice having a phenotype characterized by the substantial depletion of a mature lymphocytic cell type otherwise naturally occurring in the species from which the transgenic mouse is derived. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the lymphocytic cell type which is depleted. The transgene comprised is a DNA sequence encoding a lymphatic polypeptide variant which inhibits maturation of the lymphocytic cell type.

Transgenic non-human animals depleted in a mature lymphocytic cell-type

The invention relates to a pseudorabies virus (PRV) not found in nature and having a genome containing a mutation in the protein kinase gene region and/or in the 28K gene region. The mutation is e.g. a nucleic acid substitution, deletion, insertion or inversion, or a combination thereof. The mutations are introduced, by genetic engineering techniques, into the genome of a naturally occuring PRV, preferably NIA-3. Insertions may be nucleic acid sequences encoding antigenic polypeptides characteristic of a pathogen found in pigs. The invention also relates to vaccines containing a pseudorabies virus according to the invention, and to a process for preparing such vaccines.

Mutant pseudorabies virus, and vaccines containing the same

Transgenic mice depleted in a mature lymphocytic cell-type

Transgenic mice having a phenotype characterized by the substantial absence of mature T lymphocytes otherwise naturally occurring in said mice. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the T lymphocyte which is depleted. The transgene comprises a DNA sequence encoding a T cell receptor polypeptide variant which inhibits maturation of the T lymphocyte.

Transgenic mice depleted in mature T-cells and methods for making

A thymidine kinase deficient live deletion mutant of pseudorabies virus is provided. The mutant, designated PRV783 was derived from the live deletion mutant strain 2.4N3A by deleting a 19 bp sequence from the BamHI fragment 11 of strain 2.4N3A into which had been inserted an EcoRI restriction site at a unique cleavage site in fragment 11 for the restriction endonuclease XhoI. The 19 bp deletion encompasses the inserted EcoRI site in fragment 11 of strain 2.4N3A. PRV783 is useful for preparing vaccine compositions to immunize susceptible animals against infection by pseudorabies virus.

Deletion mutant of pseudorabies virus and vaccine containing said virus

The invention relates to live deletion mutants of a herpesvirus, especially of Pseudorabies virus. The genomes of the mutants differ from the genomes of the parent strain by the presence of one or more deletions selected from a deletion in the inverted repeats, a deletion in the unique sequence, and a deletion in the thymidine kinase gene. The new deletion mutants are avirulent, do not induce latent infections, are stable and possess good immunogenic properties. The invention also relates to vaccines containing the new mutant strains.

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Spaarndam, Netherlands

Antonius J Berns